Ignite Creation Date:
2025-12-24 @ 2:43 PM
Ignite Modification Date:
2026-01-23 @ 6:27 AM
Study NCT ID:
NCT02358759
Status:
COMPLETED
Last Update Posted:
2016-01-12
First Post:
2015-01-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Management of Abnormally Fertilized Zygotes? InVitro Correction of 3PN
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007246', 'term': 'Infertility'}], 'ancestors': [{'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['EARLY_PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 22}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-06'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-01', 'completionDateStruct': {'date': '2015-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-01-11', 'studyFirstSubmitDate': '2015-01-15', 'studyFirstSubmitQcDate': '2015-02-06', 'lastUpdatePostDateStruct': {'date': '2016-01-12', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2015-02-09', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2015-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Blastocyst development', 'timeFrame': 'Day 5 embryo development for blastocyst stage', 'description': 'availability of embryos to develop for day 5 giving chance for better cells evaluation and more genetic and cytogenetic studies.'}], 'primaryOutcomes': [{'measure': 'Normal Embryos Developed', 'timeFrame': 'Day 1 or 18 hours post ICSI nucleus removal', 'description': 'At 18 hours after ICSi nucleus to be removed in-order to make genetic correction for abnormally developed embryos. Final result is normal embryos produced with 2PNs evaluated by FSIH study for 5 chromosomes.\n\nThis indicated the genetic correction process was successful process, and applicable to produce normal growing embryos.'}], 'secondaryOutcomes': [{'measure': 'Day 3 embryo available for blastomer biopsy', 'timeFrame': '1 Year', 'description': 'Availability of successful nucleus removal from zygote to be developed to active dividing embryo available for cytogenetic study.\n\nThat indicated normal embryogenesis processing'}, {'measure': '5 chromosomes FISH study', 'timeFrame': '1 Year', 'description': 'chromosomes 13, 18, 21, X and Y to be screened using fluorescence insitu hybridization (FISH). In order to check primary euploid developed with male (XY) or female (XX) embryos.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Abnormal zygote fertilization', '3PNs correction', 'Giant oocyte management', 'triploidy fertilization', 'Maternal nucleus removal'], 'conditions': ['Infertility']}, 'referencesModule': {'references': [{'pmid': '686684', 'type': 'RESULT', 'citation': 'Jacobs PA, Angell RR, Buchanan IM, Hassold TJ, Matsuyama AM, Manuel B. The origin of human triploids. Ann Hum Genet. 1978 Jul;42(1):49-57. doi: 10.1111/j.1469-1809.1978.tb00930.x.'}, {'pmid': '23271027', 'type': 'RESULT', 'citation': 'Rosenbusch B. The potential significance of binovular follicles and binucleate giant oocytes for the development of genetic abnormalities. J Genet. 2012;91(3):397-404. doi: 10.1007/s12041-012-0195-x.'}, {'pmid': '25573721', 'type': 'RESULT', 'citation': 'Wolf DP, Mitalipov N, Mitalipov S. Mitochondrial replacement therapy in reproductive medicine. Trends Mol Med. 2015 Feb;21(2):68-76. doi: 10.1016/j.molmed.2014.12.001. Epub 2014 Dec 10.'}, {'pmid': '24558137', 'type': 'RESULT', 'citation': "Vogel G. Assisted reproduction. FDA considers trials of 'three-parent embryos'. Science. 2014 Feb 21;343(6173):827-8. doi: 10.1126/science.343.6173.827. No abstract available."}, {'pmid': '24382342', 'type': 'RESULT', 'citation': 'Amato P, Tachibana M, Sparman M, Mitalipov S. Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases. Fertil Steril. 2014 Jan;101(1):31-5. doi: 10.1016/j.fertnstert.2013.11.030.'}]}, 'descriptionModule': {'briefSummary': 'In this newly developed protocol, and idea, is to manage those abnormally developed zygotes from different ART procedures.\n\nThe investigators developed the plan and requirements needed to select the target extra nucleus or pronuclei to be extruded from fertilized egg in order to maintain developing healthy normal embryo.', 'detailedDescription': 'As approved by Dyban and Baranov et al, about 15-18% of abortions caused by triploidy fertilization. One of sources for maternally triploidy is failure in the first meiotic division (Jacobs et al., 1978).\n\nOne of Digynic triploidy is developed by fertilized giant oocyte (Dyban and Baranov, 1987) {nuclear but no cytoplasmic division in an oogonium or cytoplasmic fusion of two oogonia (Austin, 1960)}.\n\nGiant oocyte characterized with bigger diameter and will distinguished polar bodies at metaphase II.\n\nB. Rosenbusch et. al. 2002, cytogenetic study showed that extra haploid maternal copy associated with MII (46,XX/ 2N ) giant oocytes as well as triploidy with fertilized giant oocytes (3N with 69,XXX or 69,XXY).\n\nFirst Mitotic division plane with polar axes studies by Scott, 2001 , shows that Pn developed closer to 2nd polar body is the maternal origin PN.\n\nGiant oocytes were collected from different IVF cycles, to be injected with normal sperm using Intracytoplasmic sperm injection (ICSI). 18 hours post ICSI arranged for fertilization evaluation and PN removal for fertilized oocyte before syngamy starts.\n\nVideo attached shows process of zygote manipulation by the way avoiding the division axis and focusing the extra maternal PN to be aspirated.\n\nPronuclear transfer in human embryos for mitochondrial DNA correction started the methodology of pronuclear manipulation, for that possibility of utilizing of 3PNs developed embryos research tools can be started. We arranged to study available received giant oocytes during IVF cycles. Accordingly we arranged for pronuclear removal followed by FISH evaluation in order to targeting Normal males embryos that insure proper extra maternal pronucleus removal.\n\nSuccessful trials of maternal PN removal for giant oocyte collected from different cases summarized in table 1. All blastocyst developed arranged for FISH, so all embryos were utilized for cytogenetic evaluation.\n\nRecommendations:\n\nFurther evaluations using STRs (Short tandem repeat ) should be used for maternal-paternal genome differentiation. NGS study is under evaluation for developed embryos for full CCS reporting and more genetic integrity. Epigenetic evaluation study recommended for triploidy corrected embryos for genetic expressions and early embryo developments as well as differentiation between paternal and maternal genomic activity.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '45 Years', 'minimumAge': '20 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Giant oocytes\n* 3 PNs developed embryos at day 1 post ICSI.\n\nExclusion Criteria:\n\n* Patient refused to involving their abnormal oocytes at our study.'}, 'identificationModule': {'nctId': 'NCT02358759', 'briefTitle': 'Management of Abnormally Fertilized Zygotes? InVitro Correction of 3PN', 'organization': {'class': 'OTHER', 'fullName': 'Al Baraka Fertility Hospital'}, 'officialTitle': 'Treatment of Abnormally Multinucleated Zygotes Before Before Division Starting.', 'orgStudyIdInfo': {'id': 'AlBarakaSD3'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Giant Oocytes after ICSI', 'description': 'abnormally produced oocyte after ART or Controlled ovarian stimulation. Correction of abnormally fertilized oocytes using nucleus removal.', 'interventionNames': ['Procedure: Correction of abnormally fertilized oocytes']}, {'type': 'ACTIVE_COMPARATOR', 'label': '3PNs zygotes developed after ICSI', 'description': 'Abnormally developed embryos these produced 3PNs. Correction of abnormally fertilized oocytes using nucleus removal.', 'interventionNames': ['Procedure: Correction of abnormally fertilized oocytes']}], 'interventions': [{'name': 'Correction of abnormally fertilized oocytes', 'type': 'PROCEDURE', 'description': 'Removing of extra developed nucleus from fertilized oocyte.', 'armGroupLabels': ['3PNs zygotes developed after ICSI', 'Giant Oocytes after ICSI']}]}, 'contactsLocationsModule': {'locations': [{'zip': '15006', 'city': 'Manama', 'state': 'Adliyah', 'country': 'Bahrain', 'facility': 'Al Baraka Fertility Hospital', 'geoPoint': {'lat': 26.22787, 'lon': 50.58565}}, {'zip': '15006', 'city': 'Sohag', 'state': 'Sohag Governorate', 'country': 'Egypt', 'facility': 'Ibn Sina IVF Center- Ibn Sina Hospital', 'geoPoint': {'lat': 26.55695, 'lon': 31.69478}}], 'overallOfficials': [{'name': 'Ahmad M Metwalley', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Al Baraka Fertility Hospital'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Ahmad Mustafa Mohamed Metwalley', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'IVF unit director', 'investigatorFullName': 'Ahmad Mustafa Mohamed Metwalley', 'investigatorAffiliation': 'Al Baraka Fertility Hospital'}}}}